2004 Fiscal Year Final Research Report Summary
Analysis of biodefence system driven by reactive oxygene and nitrogen species
| Project/Area Number |
14370062
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka City University |
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Principal Investigator |
INOUE Masayasu Osaka City University, Medicine, Professor, 大学院・医学研究科, 教授 (80040278)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Eisuke Osaka City University, Medicine, Lecturer, 大学院・医学研究科, 講師 (60211942)
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| Project Period (FY) |
2002 – 2004
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| Keywords | Free radicals / Nitric oxide / Oxidative stress / Energy metabolism / Circulation / Super system / Metamorphosis / Evolution |
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| Research Abstract |
We found that reactive oxygen (ROS) and nitrogen species (NOx) play important roles in the regulation of circulation, energy metabolism, defence against pathogens, regulation of development and remodeling of tissues in mammals and that this super system is widely preserved among various species. The aim of the present work is to elucidate the full scope of this super system and to establish new strategy by which various diseases including cancer could be prevented and/or treated successfully.
We succeeded to establish the system for the analysis and control of unstable reactive oxygen and nitrogen species in vivo. For example, enzymes, such as SOD, ascorvate oxidase, and cytochrome c were chemically modified to obtain proteinacious probes that can be selectively targeted to ischemic tissues, vascular endothelial cells, hepatocytes, renal proximal tubule cells, and reticuloendothelial cells and tissues. Using these site-directed protein probes, we successfully revealed that the super-system driven by ROS and NOx cooperatively regulates the circulation and mitochondrial energy production, and plays critical roles in the etiology of hypertension and shock. We also succeeded to control mitochondria-dependent apoptosis of a wide variety of cells in vitro and in vivo. We also analized the mechanism of metamorphosis of tadopoles, beatles and of silk worms and fund that the super-system also operates in the regulation of their metamorphosis.
Based on these information, we succeeded to control the time and velocity of apoptosis of various cells in a wide variety of animals including rodents. We also found that L-carnitine which inhibits the mitochondria-dependent apoptosis of cells successfully suppressed the occurrence of degeneration of motor neurons and skeletal muscle in mutant SOD-expressing transgenic mice, an animal model of familiar amyotropic lateral sclerosis.
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Research Products
(59 results)
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[Journal Article] Correlation between clinical characteristics and mitochondrial D-loop DNA mutations in hepatocellular carcinoma.2004
Author(s)
Tamori, A., Nishiguchi, S., Nishikawa, M., Kubo, S., Koh, N., Hirohashi, K., Shiomi, S., Inoue M.
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Journal Title
Journal of Gastroenterology 39・11
Pages: 1063-1068
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Oxidative stress underlies the mechanism for Ca2+-induced permeability trasition of mitochondria2004
Author(s)
Kanno T, Sato EF, Utsumi T, Muranaka, S., Fujita, H., Fujiwara, T., Utsumi, T., Inoue M, Utsumi K
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Journal Title
Free Radio Res 38(1)
Pages: 27-35
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Dietary nitrate inhibits stress-induced gastric mucosal injury in the rat2003
Author(s)
M.Miyoshi, Y, Minamiyama, T, S.Taketani, K, Hiramoto, E, Kasahara, EF.Sato, M
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Journal Title
Free Radical Research 37
Pages: 85-90
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Oxidative stress-induced cell death in oral neutrophils2003
Author(s)
Sato, E.F., Higashino, M., Ikeda, K., Wake, R., Matsuo, M., Utsumi, K., a
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Journal Title
Am. J. Phyiol.-Cell Physiol. 284
Pages: C1048-C1053
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Dietary nitrate inhibits stress-induced gastric mucosal injury in the rat2003
Author(s)
M.Miyoshi, Y, Minamiyama, T, S.Taketani, K, Hiramoto, E, Kasahara, EF.Sato, M, Inoue
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Journal Title
Free Radical Research 37(1)
Pages: 85-90
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oxidative stress-induced cell death in oral neutrophils2003
Author(s)
Sato, E.F., Higashino, M., Ikeda, K., Wake, R., Matsuo, M., Utsumi, K., Inoue, M.
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Journal Title
Am.J.Phyiol.-Cell Physiol. 284
Pages: C1048-C1053
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effect of Endogenously Generated Nitric Oxide on The Energy Metabolism of Peritoneal Macrophages2003
Author(s)
Miyamoto, M., Sato, E.F., Nishikawa, M., Nishizawa Y, Morii, H., Inoue, M.
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Journal Title
Physiol.Chem.Phys. & Med.NMR 36(2)
Pages: 1-11
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Smoking a a single cigarette rapidly reduces combined concentrations of nitrate and nitrite, as well as concentrations of antioxidants in plasma2002
Author(s)
M.Tsuchiya, K, Asada, E, Kasahara, EF, Sato, M.Shindo, M, Inoue
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Journal Title
Circulation 105
Pages: 1155-1157
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Oxidative stress underlies the pathogenesis of testicular atrophy induced by di(2-ethylhexyl) phthalate2002
Author(s)
Kasahara, E, Sato, EF., Miyoshi, M., Konaka, R., Hiramoto, K., Sasaki, J., Tokuda, M.
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Journal Title
Biochem. J 365
Pages: 1-8
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Effect of Endogenously Generated Nitric Oxide on The Energy Metabolism of Peritoneal Macrophages2002
Author(s)
Miyamoto, M., Sato, E.F., Nishikawa, M., Nisizawa Y, Morii, H., Inoue, M.
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Journal Title
Physiol Chem. Phys. & Med. NMR 36
Pages: 1-11
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Smoking a single cigarette rapidly reduces combined concentrations of nitrate and nitrite, as well as concentrations of antioxidants in plasma2002
Author(s)
M, Tsuchiya, K, Asada, E, Kasahara, EF, Sato, M.Shindo, M., Inoue
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Journal Title
Circulation 105(10)
Pages: 1155-1157
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oxidative stress underlies the pathogenesis of testicular atrophy induced by di (2-ethylhexyl)phthalate2002
Author(s)
Kasahara, E., Sato, EF., Miyoshi, M., Konaka, R., Hiramoto, K., Sasaki, J., Tokuda, M., Nakano, Y., Inoue M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Book] 危ない!「慢性疲労」2004
Author(s)
倉垣弘彦, 井上正康, 渡辺恭良
Total Pages
209
Publisher
NHK出版
Description
「研究成果報告書概要(和文)」より
